A systematic review and meta-analysis for the association between duration of anticoagulation therapy and the risk of venous thromboembolism in patients with lower limb superficial venous thrombosis

Q: What are the key findings of this study?

Systemic anticoagulation for 31 to 45 days yielded the lowest VTE rate of 16.2 per 100 patient-years compared to 59.7 per 100 patient-years with short-term therapy of <=14 days.

Q: What is the clinical evidence from this study?

Study design: Meta-Analysis. Population: Symptomatic lower limb superficial venous thrombosis (SVT) without concurrent DVT or PE (n=12341). Intervention: Systemic anticoagulation therapy (UFH, LMWH, fondaparinux, VKA, or DOACs) for 31 to 45 days vs. Shorter durations of anticoagulation (<=14 days, 15-30 days) or no anticoagulation (0 days). Primary outcome: Composite of any new VTE event combining symptomatic or asymptomatic SVT progression or recurrence, new DVT, and PE per 100 patient-years (95% CI 10.4-23.3).

Q: What does this research mean for the field?

Systemic anticoagulation therapy for 31 to 45 days yields the lowest VTE rate in patients with lower limb superficial venous thrombosis compared to short-term therapy of 14 days or less. Novelty: ClaimNovelty.SYNTHESIS. Consensus alignment: ConsensusAlignment.NEUTRAL.

Kirill Victorovich Lobastov; Emel Dubar; Ilya Schastlivtsev; Astanda Bargandzhiya

doi:10.1016/j.jvsv.2023.101726

November 24, 2023Journal of Vascular Surgery Venous and Lymphatic DisordersOpen Access

A systematic review and meta-analysis for the association between duration of anticoagulation therapy and the risk of venous thromboembolism in patients with lower limb superficial venous thrombosis

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Key result

Systemic anticoagulation for 31-45 days cuts VTE to ~16 per 100 patient-years vs. shorter courses.

95% CI 10.4-23.3
n=12,341

Why the study?

The association between the duration of systemic anticoagulation therapy and the risk of further venous thromboembolism in patients with lower limb superficial venous thrombosis needed to be determined.

Does prolonged duration of systemic anticoagulation therapy reduce the risk of venous thromboembolism in patients with lower limb superficial venous thrombosis within mid-term follow-up?

Study Design

Type

Meta-Analysis (n=12,341)

Structured PICO

Does prolonged duration of systemic anticoagulation therapy reduce the risk of venous thromboembolism in patients with lower limb superficial venous thrombosis within mid-term follow-up?

P

Population

12,341 patients across 24 studies (mean age 59 years) with objectively confirmed symptomatic lower limb superficial venous thrombosis without concurrent DVT or PE, followed for a mean of 169 days (range 74-1,026 days).

I

Intervention

Systemic anticoagulation therapy (unfractionated heparin, low-molecular-weight heparin, fondaparinux, vitamin K antagonists, or direct oral anticoagulants such as rivaroxaban) at prophylactic, intermediate, or therapeutic doses stratified by treatment duration: <=14 days, 15 to 30 days, 31 to 45 days, and >45 days (range 3 to 200 days).

C

Comparator

Different anticoagulation duration subgroups (<=14 days, 15-30 days, 31-45 days, >45 days) and no systemic anticoagulation (0 days, including placebo arms in RCTs or cohorts with <10% anticoagulation use).

O

Outcome

Composite venous thromboembolism (VTE) rate per 100 patient-years, combining symptomatic or asymptomatic SVT progression or recurrence with new deep vein thrombosis (DVT) or pulmonary embolism (PE), objectively confirmed by imaging (duplex ultrasound, phlebography, CTPA, V/Q scan, or pulmonary angiography) within a mid-term follow-up of >=45 days.composite

Main Result

Absolute Event Rate: 16.2% vs 59.7%

Limitations

Heterogeneity in primary outcome definition across original trials, as not all papers reported individual outcomes
Combined data from RCTs and cohort studies of varying quality without statistical testing of differences between duration subgroups
Pooled proportions were based on study-level data rather than individual patient data, and patient-years were estimated from intended or median follow-up
High statistical heterogeneity across most calculations (I2 = 94.14% for overall primary outcome) and confirmed publication bias (Egger's test P < .001)
Events occurring within follow-up included both on- and off-anticoagulation periods, and information on post-anticoagulation surgical varicose vein treatment was unavailable
Primary outcome combined SVT progression/recurrence, DVT, and PE, but not all studies reported individual components, introducing heterogeneity
Data from RCTs and cohort studies of varying quality were combined without direct statistical testing of differences between duration groups
Pooled proportions were derived from study-level data rather than individual patient data, with patient-months/years estimated from intended or median follow-up
Events included both on- and off-treatment periods, and post-anticoagulation interventions such as varicose vein surgery were not captured
High heterogeneity across pooled estimates (I² = 94.14%) and significant publication bias (Egger's test p < 0.001)

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Implication

Prolonged systemic anticoagulation for 31 to 45 days in patients with lower limb superficial venous thrombosis is associated with the lowest rates of composite VTE and SVT recurrence without increasing major bleeding compared to shorter treatment courses.

Abstract

OBJECTIVE: The aim of this study was to determine the association between the duration of systemic anticoagulation therapy (ACT) and the risk of further venous thromboembolism (VTE) in patients with superficial venous thrombosis (SVT). METHODS: A systematic review and meta-analysis were performed using searches of Medline and Cochrane Library databases in September 2023. Papers that provided VTE incidence within mid-term follow-up of ≥45 days in patients who received any ACT were included. Patients were categorized into subgroups according to the course of treatment: (1) no ACT (0 days); (2) ACT of ≤14 days; (3) ACT of 15 to 30 days; (4) ACT of 31 to 45 days; and (5) ACT of >45 days. Reported events were transformed to events per 100 patient-years, and a random-effects model was used to calculate pooled rates for proportions. The primary outcome (VTE) was a combination of SVT progression or recurrence with the occurrence of deep vein thrombosis (DVT) and pulmonary embolism (PE). Secondary outcomes included major and clinically relevant non-major or minor bleeding. RESULTS: Twenty-four studies (10 randomized controlled trials and 14 cohort studies) combining outcomes in 12,341 patients were included in the quantitative synthesis. Minimum VTE and SVT recurrence or progression rates were observed with the ACT duration of 31 to 45 days of 16.2 (95% confidence interval [CI], 10.4-23.3) and 8.2 (95% CI, 3.1-15.8) events per 100 patient-years, respectively. Minimum DVT and PE rates observed with the treatment duration of 15 to 30 days were 5.5 (95% CI, 2.8-9.1) and 0.9 (95% CI, 0.5-1.3) events per 100 patient-years, respectively. Short-term treatment of ≤14 days was associated with the highest rates of VTE of 59.7 (95% CI, 37.7-86.4), DVT of 13.7 (95% CI, 9.6-18.4), and PE of 3.1 (95% CI, 1.4-5.6) events per 100 patient-years. Major bleeding rates were unrelated to the duration of ACT and did not exceed 0.5 events per 100 patient-years. The highest rate of clinically relevant non-major or minor bleeding was observed with ACT duration of 31 to 45 days of 14.2 (95% CI, 5.5-26.8) events per 100 patient-years. The most common risk factors for VTE included male sex, cancer, personal history of DVT, PE, or SVT, and thrombosis of non-varicose veins. CONCLUSIONS: Prolonged systemic anticoagulation is associated with the tendency to decrease VTE rates in patients with lower limb SVT.

Discussion

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Cite This Study

Lobastov et al. (2023) conducted a meta-analysis in Symptomatic lower limb superficial venous thrombosis (SVT) without concurrent DVT or PE (n=12,341). Systemic anticoagulation therapy (UFH, LMWH, fondaparinux, VKA, or DOACs) for 31 to 45 days vs. Shorter durations of anticoagulation (<=14 days, 15-30 days) or no anticoagulation (0 days) was evaluated on Composite of any new VTE event combining symptomatic or asymptomatic SVT progression or recurrence, new DVT, and PE per 100 patient-years (95% CI 10.4-23.3). Systemic anticoagulation for 31 to 45 days yielded the lowest VTE rate of 16.2 per 100 patient-years compared to 59.7 per 100 patient-years with short-term therapy of <=14 days.

synapsesocial.com/papers/6ac5b9ea67ea127fecab8055 https://doi.org/10.1016/j.jvsv.2023.101726

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A systematic review and meta-analysis for the association between duration of anticoagulation therapy and the risk of venous thromboembolism in patients with lower limb superficial venous thrombosis

Study Design

Structured PICO

Main Result

Limitations

Ask about this paper

Implication

Abstract

Discussion

Cite This Study

A systematic review and meta-analysis for the association between duration of anticoagulation therapy and the risk of venous thromboembolism in patients with lower limb superficial venous thrombosis

Study Design

Structured PICO

Main Result

Limitations

Ask about this paper

Implication

Abstract

Discussion

Cite This Study

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